Inhibition of activation of dsRNA-dependent protein kinase and tumour growth inhibition

Inhibition of dsRNA-activated protein kinase (PKR), not only attenuates muscle atrophy in a murine model of cancer cachexia (MAC16), but it also inhibits tumour growth. In vitro the PKR inhibitor maximally inhibited growth of MAC16 tumour cells at a concentration of 200 nM, which was also maximally effective in attenuating phosphorylation of PKR and of eukaryotic initiation factor (eIF)2 on the α-subunit. There was no effect on the growth of the MAC13 tumour, which does not induce cachexia, even at concentrations up to 1,000 nM. There was constitutive phosphorylation of PKR and eIF2α in the MAC16, but not in the MAC13 tumour, while levels of total PKR and eIF2α were similar. There was constitutive upregulation of nuclear factor-κB (NF-κB) in the MAC16 tumour only, and this was attenuated by the PKR inhibitor, suggesting that it arose from activation of PKR. In MAC16 alone the PKR inhibitor also attenuated expression of the 20S proteasome. The PKR inhibitor potentiated the cytotoxicity of both 5-fluorouracil and gemcitabine to MAC16 cells in vitro. These results suggest that inhibitors of PKR may be useful therapeutic agents against tumours showing increased expression of PKR and constitutive activation of NF-κB, and may also prove useful in sensitising tumours to standard chemotherapeutic agents.     

Terahertz sensing in corneal tissues

This work introduces the potential application of terahertz (THz) sensing to the field of ophthalmology, where it is uniquely suited due to its nonionizing photon energy and high sensitivity to water content. Reflective THz imaging and spectrometry data are reported on ex-vivo porcine corneas prepared with uniform water concentrations using polyethylene glycol (PEG) solutions. At 79% water concentration by mass, the measured reflectivity of the cornea was 20.4%, 14.7%, 11.7%, 9.6%, and 7.4% at 0.2, 0.4, 0.6, 0.8, and 1 THz, respectively. Comparison of nine corneas hydrated from 79.1% to 91.5% concentration by mass demonstrated an approximately linear relationship between THz reflectivity and water concentration, with a monotonically decreasing slope as the frequency increases. The THz-corneal tissue interaction is simulated with a Bruggeman model with excellent agreement. THz applications to corneal dystrophy, graft rejection, and refractive surgery are examined from the context of these measurements.     

Neurocognitive Impairment and HIV Risk Factors: A Reciprocal Relationship

Cognitive impairment among populations at risk for HIV poses a significant barrier to managing risk behaviors. The impact of HIV and several cofactors, including substance abuse and mental illness, on cognitive function is discussed in the context of HIV risk behaviors, medication adherence, and risk-reduction interventions. Literature suggests that cognitive impairment is intertwined in a close, reciprocal relationship with both risk behaviors and medication adherence. Not only do increased risk behaviors and suboptimal adherence exacerbate cognitive impairment, but cognitive impairment also reduces the effectiveness of interventions aimed at optimizing medication adherence and reducing risk. In order to be effective, risk-reduction interventions must therefore take into account the impact of cognitive impairment on learning and behavior.     

Is memory impairment greater than cognitive impairment in moderate chronic alcoholics?

The aims of the research were to test (i) whether moderate chronic alcoholics (A/pts) perform worse than non teetotaler controls (C/pts) either on memory or on intelligence tasks or on both, and (ii) whether there was a significant difference between verbal and spatial memory scores pointing to the claimed prevailing right hemisphere sensitivity to alcohol abuse. Great care was taken in selecting C/pts not to exaggerate by sample biasing the psychological effects of alcoholism. Intelligence was tested by means of verbal and performance Wechsler-Bellevue IQ and Raven PM47; memory was tested by means of serial immediate memory span and learning by means of verbal and spatial devices. The results support the conclusion that chronic wine alcoholism in a band of drinkers with lowish educational background and very set drinking habits impairs memory and intelligence without any significant difference. Moreover there is no evidence of a prevalent right hemisphere sensitivity to chronic alcohol addiction.